Pre-demential Motoric Cognitive Risk Syndrome in Ageing Subjects

Recruiting

• Conditions: Dementia; Alzheimer Disease; Motoric Cognitive Risk Syndrome; Mild Cognitive Impairment
• Interventions: Procedure: MRI evaluation; Behavioral: Actimetry & IMU; Behavioral: Gait evaluation; Behavioral: Neuropsychological evaluation

• Registration Number: NCT05640141
• Lead Sponsor: University Hospital, Caen

Brief Summary

The main aim of the study is to characterize and understand the pathological mechanisms underlying the motoric cognitive risk syndrome, which is a predictor of Alzheimer disease.

Detailed Description

Alzheimer's disease (AD) is affecting more than 46.8 million people worldwide, making dementia one of the greatest public health challenges of the 21st century. The progression of AD is slow with a presymptomatic course over several years to decades, during which pathophysiological changes are underway, but the disease has not yet caused any noticeable symptoms to warrant a clinical diagnosis. A strong effort is ongoing to identify biomarkers preceding cognitive decline that can aid diagnosis and early intervention. Criteria for the motoric cognitive risk syndrome (MCR), including subjective cognitive decline (SCD) and slower preferred walking speed, but otherwise normal functioning, are powerful risk indicators of developing cognitive impairment and dementia. The presence of MCR is associated with a more than three-fold risk of developing dementia while the risk is only two-fold for SCD or slow gait alone. However, the pathophysiology of MCR is unknown and getting into the processes that cause such condition is needed to complement the MCR-based criteria and increase their predictive validity of cognitive decline and dementia. Impaired attentional control related to white matter alterations of presumed vascular origin may be responsible for the MCR phenotype. Individuals with SCD exhibit loss of white matter integrity in brain regions typically involved in attentional control, and abnormally slow gait has been linked to the disruption of white matter tracts associated with executive attention. Furthermore, a deeper understanding of MCR requires considering not only regional white matter changes but also the individuals' cognitive capacity to cope with brain damages, namely the cognitive reserve. Hence, the PRESAGE project intends to evaluate the interplay of white matter integrity and cognitive reserve on attentional control in MCR and non-MCR individuals aged 60 or older. Attentional control will be explored at both the behavioral and brain levels using dual-task challenges where individuals will have to divide attention between a cognitive (stroop) task and a motor task (walking). The working hypothesis is that the dual-task cost - a proxy of attentional control - is predictive of white matter abnormalities which, when adjusted for cognitive reserve, age and sex, should discriminate between MCR and non-MCR individuals. The project also includes a prospective, longitudinal study (two-year follow-up) whose purpose is to determine whether this marker, alone or in combination with other potentially relevant markers (i.e., neuropsychological, functional and chronobiological), have predictive value for conversion from MCR to mild cognitive impairment and dementia. Findings will increase knowledge about the pathophysiology of MCR and will contribute to improve MCR criteria and early identification of at-risk individuals.

Study Timeline

• Status Verified: 2021-12
• Study Start: 2022-01-26
• Study First Submitted: 2022-11-28
• Study First Submitted QC: 2022-11-28
• Last Update Submitted: 2022-11-28
• Study First Posted: 2022-12-07
• Last Update Posted: 2022-12-07
• Primary Completion: 2023-12-30
• Study Completion: 2024-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Motoric Cognitive Syndrom	Gait evaluation	MCR group composed of 80 MCR participants.
Control	MRI evaluation	Control group composed of 80 healthy aged volunteers.
Control	Gait evaluation	Control group composed of 80 healthy aged volunteers.
Motoric Cognitive Syndrom	MRI evaluation	MCR group composed of 80 MCR participants.
Motoric Cognitive Syndrom	Actimetry & IMU	MCR group composed of 80 MCR participants.
Control	Actimetry & IMU	Control group composed of 80 healthy aged volunteers.
Control	Neuropsychological evaluation	Control group composed of 80 healthy aged volunteers.
Motoric Cognitive Syndrom	Neuropsychological evaluation	MCR group composed of 80 MCR participants.

Primary Outcome Measures

Name	Time	Method
Prediction accuracy to detect MCR participants will be computed using Machine learning	Baseline	Several machine learning algorithms will be used to tell apart healthy from MCR participants. These classification procedures will bring several metrics including prediction accuracy, sensitivity and specificity scores.

Secondary Outcome Measures

Name	Time	Method
MRI - Connectivity	Baseline	Brain connectivity (covariation patterns) in each group will be computed.
MRI - Brain volumes	Baseline	Grey and white matter atrophy, grey matter structural covariation and white matter hyperintensity will be assessed.
Gait - Dual task cost	Baseline	Difference in spatio-temporal and non-linear gait parameters bewteen simple and dual task / between groups
Gait - Sensorimotor adaptation and savings	Baseline	Difference in terms of sensorimotor adaptation on split-belt treadmill bewteen groups

Trial Locations

Locations (1)

CHU de Caen Normandie; 🇫🇷 Caen, France